tbuckley/cabot-search huggingface dataset:
Evaluation of Out-of-Pocket Costs and Treatment Intensification With an SGLT2 Inhibitor or GLP-1 RA in Patients With Type 2 Diabetes and Cardiovascular Disease
Authors: Jing Luo, Robert Feldman, Katherine Callaway Kim, Scott Rothenberger, Mary Korytkowski, Inmaculada Hernandez, Walid F. Gellad
Journal: JAMA Network Open (2023)

Importance The latest guidelines continue to recommend sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD). Despite this, overall use of these 2 drug classes has been suboptimal. Objective To assess the association of high out-of-pocket (OOP) costs and the initiation of an SGLT2 inhibitor or GLP-1 RA among adults with T2D and established CVD who are treated with metformin-treated. Design, Setting, and Participants This retrospective cohort study used 2017 to 2021 data from the Optum deidentified Clinformatics Data Mart Database. Each individual in the cohort was categorized into quartiles of OOP costs for a 1-month supply of SGLT2 inhibitor and GLP-1 RA based on their health plan assignment. Data were analyzed from April 2021 to October 2022. Exposures OOP cost for SGLT2 inhibitors and GLP-1 RA. Main Outcomes and Measures The primary outcome was treatment intensification, defined as a new dispensing (ie, initiation) of either an SGLT2 inhibitor or GLP-1 RA, among patients with T2D previously treated with metformin monotherapy. For each drug class separately, Cox proportional hazards models were used to adjust for demographic, clinical, plan, clinician, and laboratory characteristics to estimate the hazard ratios of treatment intensification comparing the highest vs the lowest quartile of OOP costs. Results Our cohort included 80 807 adult patients (mean [SD] age, 72 [9.5] years, 45 129 [55.8%] male; 71 128 [88%] were insured with Medicare Advantage) with T2D and established CVD on metformin monotherapy. Patients were followed for a median (IQR) of 1080 days (528 to 1337). The mean (SD) of OOP costs in the highest vs lowest quartile was $118 [32] vs $25 [12] for GLP-1 RA, and $91 [25] vs $23 [9] for SGLT2 inhibitors. Compared with patients in plans with the lowest quartile (Q1) of OOP costs, patients in plans with the highest quartile (Q4) of costs were less likely to initiate a GLP-1 RA (adjusted HR, 0.87 [95% CI, 0.78 to 0.97]) or an SGLT2 inhibitor (adjusted HR, 0.80 [95% CI, 0.73 to 0.88]). The median (IQR) number of days to initiating a GLP-1 RA was 481 (207-820) days in Q1 and 556 (237-917) days in Q4 of OOP costs and 520 (193-876) days in Q1 vs 685 (309-1017) days in Q4 for SGLT2 inhibitors. Conclusions and Relevance In this cohort study of more than 80 000 older adults with T2D and established CVD covered by Medicare Advantage and commercial plans, those in the highest quartile of OOP cost were 13% and 20% less likely to initiate a GLP-1 RA or SGLT2 inhibitor, respectively, when compared with those in the lowest quartile of OOP costs.
Evaluation of Oseltamivir Used to Prevent Hospitalization in Outpatients With Influenza
Authors: Ryan Hanula, Émilie Bortolussi-Courval, Arielle Mendel, Brian J. Ward, Todd C. Lee, Emily G. McDonald
Journal: JAMA Internal Medicine (2023)

Importance Despite widespread use, summary evidence from prior meta-analyses has contradictory conclusions regarding whether oseltamivir decreases the risk of hospitalization when given to outpatients. Several large investigator-initiated randomized clinical trials have not yet been meta-analyzed. Objective To assess the efficacy and safety of oseltamivir in preventing hospitalization among influenza-infected adult and adolescent outpatients. Data Sources PubMed, Ovid MEDLINE, Embase, Europe PubMed Central, Web of Science, Cochrane Central, ClinicalTrials.gov, and WHO International Clinical Trials Registry were searched from inception to January 4, 2022. Study Selection Included studies were randomized clinical trials comparing oseltamivir vs placebo or nonactive controls in outpatients with confirmed influenza infection. Data Extraction and Synthesis In this systematic review and meta-analysis, Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were followed. Two independent reviewers (R.H. and É.B.C.) extracted data and assessed risk of bias using the Cochrane Risk of Bias Tool 2.0. Each effect size was pooled using a restricted maximum likelihood random effects model. The quality of evidence was graded using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework. Main Outcomes and Measures Hospitalization was pooled as risk ratio (RR) and risk difference (RD) estimates with 95% CIs. Results Of 2352 studies identified, 15 were included. The intention-to-treat infected (ITTi) population was comprised of 6166 individuals with 54.7% prescribed oseltamivir. Across study populations, 53.9% (5610 of 10 471) were female and the mean age was 45.3 (14.5) years. Overall, oseltamivir was not associated with reduced risk of hospitalization within the ITTi population (RR, 0.79; 95% CI, 0.48 to 1.29; RD, −0.17%; 95% CI, −0.23% to 0.48%). Oseltamivir was also not associated with reduced hospitalization in older populations (mean age ≥65 years: RR, 1.01; 95% CI, 0.21 to 4.90) or in patients considered at greater risk of hospitalization (RR, 0.65; 0.33 to 1.28). Within the safety population, oseltamivir was associated with increased nausea (RR, 1.43; 95% CI, 1.13 to 1.82) and vomiting (RR, 1.83; 95% CI, 1.28 to 2.63) but not serious adverse events (RR, 0.71; 95% CI, 0.46 to1.08). Conclusions and Relevance In this systematic review and meta-analysis among influenza-infected outpatients, oseltamivir was not associated with a reduced risk of hospitalization but was associated with increased gastrointestinal adverse events. To justify continued use for this purpose, an adequately powered trial in a suitably high-risk population is justified.
Probing Deeper Into the Association Between Acid-Suppressive Medication Use and Allergic Diseases—Reply
Authors: Yunha Noh, Ju-Young Shin
Journal: JAMA Pediatrics (2023)

In Reply We thank Hsieh and Lin for their interest in our study1 on the association between prenatal and infant exposure to acid-suppressive medications (ASM) and the risk of allergic diseases in children. We have responded to their comments as follows.
Association of Early Hysterectomy With Risk of Cardiovascular Disease in Korean Women
Authors: Jin-Sung Yuk, Byung Gyu Kim, Byoung Kwon Lee, Jongkwon Seo, Gwang Sil Kim, Kyongjin Min, Hye Young Lee, Young Sup Byun, Byung Ok Kim, Seung-Woo Yang, Myoung-Hwan Kim, Sang-Hee Yoon, Yong-Soo Seo
Journal: JAMA Network Open (2023)

Women who undergo surgical hysterectomy before natural menopause may have an earlier increase in hematocrit and storage iron levels than those who continue menstruation, thereby increasing the risk of cardiovascular disease (CVD) at ages younger than usually seen. Examining this issue may provide important implications for women's cardiovascular health to both physicians and patients.To evaluate the association of hysterectomy with the risk of incident CVD among women before age 50 years.In this Korean population-based cohort study, 135 575 women aged 40 to 49 years were evaluated from January 1, 2011, to December 31, 2014. After propensity score matching in covariates including age, socioeconomic status, region, Charlson Comorbidity Index, hypertension, diabetes, dyslipidemia, menopause, menopausal hormone therapy, and adnexal surgery before inclusion, 55 539 pairs were included in the hysterectomy and nonhysterectomy groups. Participants were followed up until December 31, 2020. Data analysis was conducted from December 20, 2021, to February 17, 2022.The primary outcome was an incidental CVD, a composite of myocardial infarction, coronary artery revascularization, and stroke. The individual components of the primary outcome were also evaluated.A total of 55 539 pairs were included; median age in the combined groups was 45 (IQR, 42-47) years. During median follow-up periods in the hysterectomy group of 7.9 (IQR, 6.8-8.9) years and nonhysterectomy group of 7.9 (IQR, 6.8-8.8) years, the incidence of CVD was 115 per 100 000 person-years for the hysterectomy group and 96 per 100 000 person-years for the nonhysterectomy group. After adjusting for confounding factors, the hysterectomy group had an increased risk of CVD compared with the nonhysterectomy group (hazard ratio [HR], 1.25; 95% CI, 1.09-1.44). The incidences of myocardial infarction and coronary artery revascularization were comparable between the groups, whereas the risk of stroke was significantly higher in the hysterectomy group (HR, 1.31; 95% CI, 1.12-1.53). Even after excluding women who underwent oophorectomy, the hysterectomy group had higher risks of CVD (HR, 1.24; 95% CI, 1.06-1.44).The findings of this cohort study suggest early menopause owing to hysterectomy was associated with increased risks for a composite of CVD, particularly stroke.
Sm/Co‐Doped Silica‐Based Nanozymes Reprogram Tumor Microenvironment for ATP‐Inhibited Tumor Therapy
Authors: Siyi Li, He Ding, Jinghu Chang, Shikai Liu, Shuming Dong, Mikhail V. Zyuzin, Alexander S. Timin, Lili Feng, Fei He, Shili Gai, Piaoping Yang
Journal: Advanced Healthcare Materials (2023)

Current applications of multifunctional nanozymes for reprogramming the redox homeostasis of the tumor microenvironment (TME) have been severely confronted with low catalytic activity and the ambiguity of active sites of nanozymes, as well as the stress resistance from the rigorous physical environment of tumor cells. Herein, the Sm/Co-doped mesoporous silica with 3PO-loaded nanozymes (denoted as mSC-3PO) are rationally constructed for simultaneously inhibiting energy production by adenosine triphosphate (ATP) inhibitor 3PO and reprogramming TME by multiactivities of nanozymes with photothermal effect assist, i.e., enhanced peroxidase-like, catalase-like activity, and glutathione peroxidase-like activities, facilitating reactive oxygen species (ROS) generation, promoting oxygen content, and restraining the over-expressed glutathione. Through the optimal regulation of nanometric size and doping ratio, the fabricated superparamagnetic mSC-3PO enables the excellent exposure of active sites and avoids agglomeration owing to the large specific surface and mesoporous structure, thus providing adequate Sm/Co-doped active sites and enough spatial distribution. The constructed Sm/Co centers both participate in the simulated biological enzyme reactions and carry out the double-center catalytic process (Sm3+ and Co3+ /Co2+ ). Significantly, as the inhibitor of glycolysis, 3PO can reduce the ATP flow by cutting down the energy transform, thereby inhibiting tumor angiogenesis and assisting ROS to promote the early withering of tumor cells. In addition, the considerable near-infrared (NIR) light absorption of mSC-3PO can adapt to NIR excitable photothermal treatment therapy and photoexcitation-promoted enzymatic reactions. Taken together, this work presents a typical therapeutic paradigm of multifunctional nanozymes that simultaneously reprograms TME and promotes tumor cell apoptosis with photothermal assistance.
Keeping it in the family: HER3 as a target in brain metastases
Authors: Sheheryar Kabraji, Nancy U. Lin
Journal: Clinical Cancer Research (2023)

Summary In 180 patients with metastatic breast cancer and non–small cell lung cancer (NSCLC), HER3 expression was found in &amp;gt;70% of brain metastases (BM). HER3-targeting antibody–drug conjugates have demonstrated efficacy in HER3-expressing metastatic breast cancer and NSCLC. Thus, HER3 expression by IHC may be a biomarker for development of HER3-targeting BM-specific therapeutics. See related article by Tomasich et al., p. 3225
Altered intestinal microbiome and epithelial damage aggravate intestinal graft-versus-host disease
Authors: Fei Gao, Hengwei Wu, Limengmeng Wang, Yanmin Zhao, He Huang
Journal: Gut Microbes (2023)

Despite significant achievements in hematopoietic stem cell transplantation (HSCT), graft-versus-host disease (GVHD), especially intestinal GVHD, remains a major obstacle to this procedure. GVHD has long been regarded as a pathogenic immune response, and the intestine has been simply considered as a target of immune attack. In effect, multiple factors contribute to intestinal damage after transplantation. Impaired intestinal homeostasis including altered intestinal microbiome and epithelial damage results in delayed wound healing, amplified immune response and sustained tissue destruction, and it may not fully recover following immunosuppression. In this review, we summarize factors leading to intestinal damage and discuss the relationship between intestinal damage and GVHD. We also describe the great potential of remodeling intestinal homeostasis in GVHD management.
Introducing the <i>JAMA Pediatrics</i> Editorial Fellowship
Authors: Dimitri A. Christakis, Andrea F. Duncan
Journal: JAMA Pediatrics (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Syk Inhibition Reprograms Tumor-Associated Macrophages and Overcomes Gemcitabine-Induced Immunosuppression in Pancreatic Ductal Adenocarcinoma
Authors: Deepak Rohila, In Hwan Park, Timothy V. Pham, Jonathan Weitz, Tatiana Hurtado de Mendoza, Suresh Madheswaran, Mehreen Ishfaq, Cooper Beaman, Elisabette Tapia, Siming Sun, Jay Patel, Pablo Tamayo, Andrew M. Lowy, Shweta Joshi
Journal: Cancer Research (2023)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is an insidious disease with a low 5-year survival rate. PDAC is characterized by infiltration of abundant tumor-associated macrophages (TAM), which promote immune tolerance and immunotherapeutic resistance. Here we report that macrophage spleen tyrosine kinase (Syk) promotes PDAC growth and metastasis. In orthotopic PDAC mouse models, genetic deletion of myeloid Syk reprogrammed macrophages into immunostimulatory phenotype, increased the infiltration, proliferation, and cytotoxicity of CD8+ T cells, and repressed PDAC growth and metastasis. Furthermore, gemcitabine (Gem) treatment induced an immunosuppressive microenvironment in PDAC by promoting protumorigenic polarization of macrophages. In contrast, treatment with the FDA-approved Syk inhibitor R788 (fostamatinib) remodeled the tumor immune microenvironment, “re-educated” protumorigenic macrophages towards an immunostimulatory phenotype and boosted CD8+ T-cell responses in Gem-treated PDAC in orthotopic mouse models and an ex vivo human pancreatic slice culture model. These findings illustrate the potential of Syk inhibition for enhancing the antitumor immune responses in PDAC and support the clinical evaluation of R788 either alone or together with Gem as a potential treatment strategy for PDAC. Significance: Syk blockade induces macrophage polarization to an immunostimulatory phenotype, which enhances CD8+ T-cell responses and improves gemcitabine efficacy in pancreatic ductal adenocarcinoma, a clinically challenging malignancy.
Deletion of hepatic growth hormone receptor (GHR) alters the mouse gut microbiota by affecting bile acid metabolism
Authors: Zichao Yu, Yu Wang, Fang Zhang, Rui Ma, Xiaoyu Yang, Kun Yang, Ai Mi, Liyuan Ran, Yingjie Wu
Journal: Gut Microbes (2023)

Both growth hormone (GH) and gut microbiota play significant roles in diverse physiological processes, but the crosstalk between them is poorly understood. Despite the regulation of GH by gut microbiota, study on GH's influence on gut microbiota is limited, especially on the impacts of tissue specific GH signaling and their feedback effects on the host. In this study, we profiled gut microbiota and metabolome in tissue-specific GHR knockout mice in the liver (LKO) and adipose tissue (AKO). We found that GHR disruption in the liver rather than adipose tissue affected gut microbiota. It changed the abundance of Bacteroidota and Firmicutes at phylum level as well as abundance of several genera, such as Lactobacillus, Muribaculaceae, and Parasutterella, without affecting α-diversity. Moreover, the impaired liver bile acid (BA) profile in LKO mice was strongly associated with the change of gut microbiota. The BA pools and 12-OH BAs/non-12-OH BAs ratio were increased in the LKO mice, which was due to the induction of CYP8B1 by hepatic Ghr knockout. Consequently, the impaired BA pool in cecal content interacted with gut bacteria, which in turn increased the production of bacteria derived acetic acid, propionic acid, and phenylacetic acid that were possible to participate in the impaired metabolic phenotype of the LKO mice. Collectively, our findings suggested that the liver GH signaling regulates BA metabolism by its direct regulation on CYP8B1, which is an important factor influencing gut microbiota. Our study is significant in exploring gut microbiota modification effects of tissue-specific GH signaling as well as its involvement in gut microbiota-host interaction.
Integration of Activation by Hypoxia and Inhibition Resistance of Tumor Cells to Apoptosis for Precise and Augmented Photodynamic Therapy
Authors: Yutong Shao, Miaomiao Chen, Wenlong Chen, Zehui Wang, Mengzhang Sui, Mingyu Tian, Yingnan Wu, Jitao Song, Debin Ji, Fengling Song
Journal: Advanced Healthcare Materials (2023)

Abstract Photodynamic therapy (PDT) uses photosensitizers to convert oxygen (O 2 ) to reactive oxygen species (ROS) under irradiation to induce DNA damage and kill cancer cells. However, the effect of PDT is usually alleviated by apoptosis resistance mechanism of tumor living cells. MTH1 enzyme is known to be such an apoptosis‐resistance enzyme which is over expressed as a scavenger to repair the damaged DNA. In this work, a hypoxia‐activated nanosystem FTPA, which can be degraded to release the encapsulated PDT photosensitizer 4‐DCF‐MPYM and an inhibitor TH588 is proposed. The inhibitor TH588 can inhibit the DNA repair process by reducing the activity of MTH1 enzyme, and achieve the purpose of amplifying the therapeutic effect of PDT. This work demonstrates that a precise and augmented tumor PDT is achieved by integration of hypoxia‐activation and inhibition resistance of tumor cells to apoptosis.
Dynamic associations between the respiratory tract and gut antibiotic resistome of patients with COVID-19 and its prediction power for disease severity
Authors: Yifei Shen, Wenxin Qu, Fei Yu, Dan Zhang, Qianda Zou, Dongsheng Han, Mengxiao Xie, Xiao Chen, Lingjun Yuan, Bin Lou, Guoliang Xie, Ruonan Wang, Xianzhi Yang, Weizhen Chen, Qi Wang, Yun Teng, Yuejiao Dong, Li Huang, Jiaqi Bao, Chang Liu, Wei Wu, Enhui Shen, Longjiang Fan, Michael P. Timko, Shufa Zheng, Yu Chen
Journal: Gut Microbes (2023)

The antibiotic resistome is the collection of all antibiotic resistance genes (ARGs) present in an individual. Whether an individual's susceptibility to infection and the eventual severity of coronavirus disease 2019 (COVID-19) is influenced by their respiratory tract antibiotic resistome is unknown. Additionally, whether a relationship exists between the respiratory tract and gut ARGs composition has not been fully explored. We recruited 66 patients with COVID-19 at three disease stages (admission, progression, and recovery) and conducted a metagenome sequencing analysis of 143 sputum and 97 fecal samples obtained from them. Respiratory tract, gut metagenomes, and peripheral blood mononuclear cell (PBMC) transcriptomes are analyzed to compare the gut and respiratory tract ARGs of intensive care unit (ICU) and non-ICU (nICU) patients and determine relationships between ARGs and immune response. Among the respiratory tract ARGs, we found that Aminoglycoside, Multidrug, and Vancomycin are increased in ICU patients compared with nICU patients. In the gut, we found that Multidrug, Vancomycin, and Fosmidomycin were increased in ICU patients. We discovered that the relative abundances of Multidrug were significantly correlated with clinical indices, and there was a significantly positive correlation between ARGs and microbiota in the respiratory tract and gut. We found that immune-related pathways in PBMC were enhanced, and they were correlated with Multidrug, Vancomycin, and Tetracycline ARGs. Based on the ARG types, we built a respiratory tract-gut ARG combined random-forest classifier to distinguish ICU COVID-19 patients from nICU patients with an AUC of 0.969. Cumulatively, our findings provide some of the first insights into the dynamic alterations of respiratory tract and gut antibiotic resistome in the progression of COVID-19 and disease severity. They also provide a better understanding of how this disease affects different cohorts of patients. As such, these findings should contribute to better diagnosis and treatment scenarios.
Epidemiology of Cancer-Associated Venous Thromboembolism in Patients With Solid and Hematologic Neoplasms in the Veterans Affairs Health Care System
Authors: Kylee L. Martens, Ang Li, Jennifer La, Sarah B. May, Kaitlin N. Swinnerton, Hannah Tosi, Danne C. Elbers, Nhan V. Do, Mary T. Brophy, J. Michael Gaziano, Saran Lotfollahzadeh, Vipul Chitalia, Katya Ravid, Nathanael R. Fillmore
Journal: JAMA Network Open (2023)

Identifying changes in epidemiologic patterns of the incidence and risk of cancer-associated thrombosis (CAT), particularly with evolving cancer-directed therapy, is essential for risk stratification.